The compound imiquimod, [3-(2-methylpropyl)-3,5,8-triazatricyclo[7.4.0.02.6]trideca-1(9),2(6),4,7,10,12-hexaen-7-amine] is incorporated in a topical cream formulation for the treatment of skin lesions associated with actinic keratosis, basal cell carcinoma and anogenital warts.
Due to reactions in the formulation between some of the excipients and the preservatives, the formulation does not consistently comply with the British Pharmacopoeia preservative efficacy test. Because of this, therapeutic regulatory bodies limit the sale of the formulation to single-dose sachets in all countries where compliance with the British Pharmacopoeia test is mandatory. These formulations are presently sold in sets of six or 12 single-dose laminated sachets in Australia and other countries. The sachets comprise 250 mg of 5% w/w imiquimod cream.
The area and location of the lesions treated by the formulation vary according to the condition and its severity. This makes correct dosing of the cream difficult. For example, actinic keratosis (also known as solar keratosis) generally appears on areas of the body exposed to excessive sunlight such as the head, neck and the back of the hands. In severe cases there may be many lesions spread over a comparatively large area such as the entire scalp and forehead. Similarly basal cell carcinomas (BCC) may occur at various locations on the body whereas genital warts occur around the genital or anogenital region. Due to potential side effects of the cream, patients are warned to confine the treatment area to no larger than 20 cm2. With conditions such as actinic keratosis where lesions may be spread over a relatively large part of the body, patients may be tempted to apply too much of the formulation. In contrast, in the case of small or less numerous lesions such as genital warts, the patient may apply too little of the formulation.
In addition to the above dosage difficulties, further difficulties arise because patients presently use a sachet more than once despite the manufacturer's warning not to re-use a sachet. The open sachet must be refrigerated to prevent microbial growth in case the remaining contents have been contaminated during use. As will be appreciated, contamination is a risk because some patients may not practice good hygiene. Depending on where and how the patient applies cream, this may increase the likelihood of contamination. Exposure to air may also adversely affect the cream. Further, access to refrigeration may be an issue where a patient is travelling or away from home. It may be embarrassing for a patient to have to ask a host to refrigerate a sachet, particularly for someone who is treating genital warts.
Statements made above about the prior art should not be taken to mean that the prior art discussed is part of the common general knowledge in the field, whether in Australia or elsewhere.
The present invention addresses at least some of the difficulties associated with currently available imiquimod creams in the treatment of the conditions discussed above.